Stroke remains the third largest cause of death and is a major cause of morbidity and dementia with great healthcare expenditures on rehabilitation and long-term care and has an even higher impact on African-American and Hispanic populations. Atrial fibrillation (AF) is known to be a major cause of stroke involved in at least 20% of all ischemic strokes (cardiogenic stroke). However, there is evidence that AF is a significantly greater cause of stroke. Several small pilot studies have shown that 15 to 23% of patients diagnosed with stroke of unknown etiology (cryptogenic stroke) have intermittent AF detected only with extra cardiac monitoring as an outpatient after the AF was not detected by intra-hospital workup. Our genetic studies with markers specific to AF and cardiogenic stroke have supported the notion that there are many stroke patients with undiagnosed AF: these widely replicated genetic markers show significant correlation to both cryptogenic and large vessel strokes in several cohorts - suggesting that 20 to 30% of cryptogenic and large vessel stroke patients actually have undiagnosed AF as the potential cause for the stroke. The prevention of another stroke due to AF is very different from secondary prevention of other strokes (warfarin vs anti-platelet drugs). However, patients with undiagnosed AF will not be adequately covered with the proper medication- extra monitoring is not occuring routinely because no large study has been run to compare the effectiveness of extra cardiac monitoring and risk stratification on improving the sensitivity of detecting AF after acute stroke compared to intrahospital workup. The 2009 IOM recommendations for comparative effectiveness research identified cardiovascular disease and arrhythmias among higher priority disease areas and set African- American and Hispanic populations as priority populations. Our comparative effectiveness study seeks to followup previous observations by: 1. Comparing rates of iAF in 500 cryptogenic stroke and large vessel stroke white patients using ambulatory cardiac monitoring compared to full intra-hospital workup alone. 2. Comparing rates of iAF in cryptogenic stroke and large vessel stroke in 500 African-American and Hispanic patients who have disproportionately high rates of stroke compared to intra- hospital workup alone. 3. Comparing rates of iAF in cryptogenic stroke and large vessel stroke patients in patients with genetic, family history, and clinical risk factors for AF versus lower risk patients. The study will recruit 1000 acute stroke patients with cryptogenic or large vessel stroke from white, African-American, and Hispanic populations in 6 JCAHO-certified acute stroke centers run by stroke neurologists with past experience with numerous clinical trials including some of the pivotal studies on AF and stroke. All participating stroke patients will be given ambulatory cardiac monitoring for 21 days. Therefore, each patient serves as the comparator to him or herself for the study of extra monitoring versus intra-hospital workup. Another 300 age- and ethnicity-matched non-stroke patients will be recruited in parallel to determine the baseline rate of iAF in the population detected by extra monitoring. Samples, genotypes, and clinical data from the well-phenotyped patients in this multi-ethnic study will be deposited in the NINDS Stroke Repository to allow other researchers to ask questions of interest to them. PUBLIC HEALTH RELEVANCE: A common abnormal heart rhythm called atrial fibrillation is known to cause about 1 in 6 strokes. However, it appears that atrial fibrillation is an even more common cause of stroke but is often not diagnosed because it is usually does not cause symptoms and it comes and goes (intermittent). Extra monitoring of the heart with lightweight devices the size of a pager may do a much better job detecting this type of stroke which may lead to a different drug to prevent recurrence of the stroke. Genetic risk markers for atrial fibrillation may help define which patients would benefit from extra cardiac monitoring to detect atrial fibrillation so that prevention strategies can be tried to prevent another stroke. Improved detection of atrial fibrillation, especially in patients who have had a recent stroke may substantially decrease both the recurrent stroke rate and the cost of healthcare.